Introduction: Central nervous system (CNS) metastases in lung cancer are a frequent cause of morbidity and mortality. There are conflicting data on the incidence of CNS metastases in stage IV ROS1‐positive NSCLC and the rate of CNS progression during crizotinib therapy. Methods: A retrospective review of 579 patients with stage IV NSCLC between June 2008 and December 2017 was performed. Brain metastases and oncogene status (ROS1, ALK receptor tyrosine kinase gene [ALK], EGFR, KRAS, BRAF, and others) were recorded. We measured progression‐free survival and time to CNS progression in ROS1‐positive and ALK‐positive patients who were taking crizotinib. Results: We identified 33 ROS1‐positive and 115 ALK‐positive patients with stage IV NSCLC. The incidences of brain metastases for treatment‐naive, stage IV ROS1‐positive and ALK‐positive NSCLC were 36% (12 of 33) and 34% (39 of 115), respectively. There were no statistically significant differences in incidence of brain metastases across ROS1, ALK, EGFR, KRAS, BRAF, or other mutations. Complete survival data were available for 19 ROS1‐positive and 83 ALK‐positive patients. The median progression‐free survival times for ROS1‐positive and ALK‐positive patients were 11 and 8 months, respectively (p = 0.304). The CNS was the first and sole site of progression in 47% of ROS1‐positive (nine of 19) and 33% of ALK‐positive (28 of 83) patients, with no statistically significant differences between these groups (p = 0.610). Conclusions: Brain metastases are common in treatment‐naive stage IV ROS1‐positive NSCLC, though the incidence does not differ from that in other oncogene cohorts. The CNS is a common first site of progression in ROS1‐positive patients who are taking crizotinib. This study reinforces the importance of developing CNS‐penetrant tyrosine kinase inhibitors for patients with ROS1‐positive NSCLC.

中文翻译：

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克唑替尼治疗IV期ROS1重排非小细胞肺癌脑转移发生率和中枢神经系统进展率

介绍：肺癌中的中枢神经系统 (CNS) 转移是发病率和死亡率的常见原因。关于 IV 期 ROS1 阳性 NSCLC 中 CNS 转移发生率和克唑替尼治疗期间 CNS 进展率的数据存在矛盾。方法：对 2008 年 6 月至 2017 年 12 月期间 579 例 IV 期 NSCLC 患者进行回顾性研究。记录脑转移和癌基因状态（ROS1、ALK 受体酪氨酸激酶基因 [ALK]、EGFR、KRAS、BRAF 等）。我们测量了服用克唑替尼的 ROS1 阳性和 ALK 阳性患者的无进展生存期和至 CNS 进展的时间。结果：我们确定了 33 名 ROS1 阳性和 115 名 ALK 阳性的 IV 期 NSCLC 患者。未经治疗的脑转移发生率，IV 期 ROS1 阳性和 ALK 阳性 NSCLC 分别为 36%（33 个中的 12 个）和 34%（115 个中的 39 个）。ROS1、ALK、EGFR、KRAS、BRAF 或其他突变的脑转移发生率没有统计学显着差异。19 名 ROS1 阳性和 83 名 ALK 阳性患者可获得完整的生存数据。ROS1 阳性和 ALK 阳性患者的中位无进展生存时间分别为 11 和 8 个月（p = 0.304）。CNS 是 47% 的 ROS1 阳性（19 名中的 9 名）和 33% 的 ALK 阳性（83 名中的 28 名）患者的第一个也是唯一的进展部位，这些组之间没有统计学显着差异（p = 0.610）。结论：脑转移在未经治疗的 IV 期 ROS1 阳性 NSCLC 中很常见，但发生率与其他癌基因队列中的发生率没有差异。在服用克唑替尼的 ROS1 阳性患者中，CNS 是常见的第一个进展部位。这项研究强调了为 ROS1 阳性 NSCLC 患者开发 CNS 渗透性酪氨酸激酶抑制剂的重要性。